Bacterial exotoxins (gram positive bacteria) including SEB are capable of inducing toxic shock in humans. SEB and other exotoxins are thought to induce toxic shock by acting as superantigens, stimulating massive systemic T-cell proliferation. The inflammatory mechanisms and chemical signals involved in mediating this response are key in elucidating the pathogenesis of exotoxin-induced toxic shock. Challenging known susceptible strains of laboratory mice with SEB and measuring the subsequent inflammatory response can be useful in investigating these mechanisms. Of the known cytokines involved, serum levels of IL-2 and TNF-alpha peak at approximately 2-hours post SEB injection and IL-6 at about 6-hours. This model can be used to examine the anti-inflammatory properties of compounds targeting the release of IL-2, TNF-alpha and IL-6.
Preclinical Drug Efficacy Studies
Mice (Susceptibility differs by strain, contact us to select an appropriate strain or to discuss a strain you are considering)
Mice are injected i.p. with SEB to induce the inflammatory response. Blood sampling is conducted at specified time points for the measurement of inflammatory cytokines. Compound administration is performed according to the study protocol.
Clinical observations, body weight, and cytokine profiling using ELISA and Luminex multiplex assays
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Miethke T, Wahl C, Heeg K, Echtenacher B, Kramer PH and Wagner H. (1992) T Cell-mediated Lethal Shock Triggered in Mice by the Superantigen Staphlococcal Enterotoxin B: Critical Role of Tumor Necrosis Factor. Journal of Experimental Medicine; 175:91-8.
Torres BA, Kominsky SP, Perrin GQ, Hobeika AC and Johnson HM. (2001) Superantigens: The Good the Bad, and the Ugly. Experimental Biological Medicine; 226(3):164-76.